Objective To investigate the physiological cascade occurring in response to cytokine administration, especially the release of cytokines within the central nervous system. To extend our prior studies on the endocrine, immune, and behavioral effects of cytokine administration, we have been assessing the cytokine cascade induced by interleukin-1. Interleukin-6 and soluble interleukin-6 receptor were measured in blood and cerebrospinal fluid following intravenous administration of interleukin-6. IL-1 induced a marked elevation in IL-6 levels in both the hematological and intrathecal compartments; increased sIL-6r levels were found ionly in the bloodstream. These observations support the hypothesis that many of IL-1's effects are mediated through IL-6, and the release of high levels of IL-6 within the CNS may account for some of the behavioral alterations seen after IL-1 administration. Key words cytokine, interleukin-1, interleukin-6, cerebrospinal fluid